There are limited data regarding the prevalence of HSV-2 infections among US adolescents. In addition, the functional mechanism and molecular targets of the initial immune responses that provide the foundation for controlling infection and promoting pathogenesis is largely unknown. Examining infection in adolescents who are presumably more immunologically "naive" and more likely to be diagnosed with a primary infection, compared to older individuals provides an important for evaluating the interaction among factors related to initial acquisition of infection, transmission, or progression to more severe sequelae including recurrent ulcers. Thus, adolescents present a unique opportunity to examine those factors which have direct relevance to vaccine development and treatment. Determining the prevalence of HSV-1 infection among adolescents and the interrelationship, if any, between seroprevalence of HSV-1 and HSV-2 will provide further important information regarding optimal HSV vaccine strategies. Specifically our aims are: 1. To determine sociodemographic and behavioral risk factors for prevalent and incident HSV-1 and HSV-2 infection among sexually active African-American adolescents. 2. To determine the natural history of cellular mediated immune responses in relation to clinical manifestations of HSV among infected individuals. We will assess the CD4 T-cell recognition of glycoproteins common to HSV-1 and HSV-2 (gB and gD), the type-specific gG2 protein and HSV-infected cell antigen, along with the Th1 and Th2 cytokine responses to stimulation with these antigens. 3. To determine immunologic risk factors for transmission of HSV-2 between adolescents and their sex partners over the course of the study among couples who are discordant on their HSV-2 serologic status. Transmission patterns will be assessed using gG2-based type-specific serologic assay, and then correlated with clinical histories of HSV infection, antibodies to heterologous virus, and duration of relationships.